Over 12 years of follow-up, those who used the cholesterol lowering medications were no more likely to develop the disease than those who did not use statins (hazard ratio: 0.91, 95% CI: 0.54 to 1.52), Zoe Arvanitakis, M.D., and colleagues from Rush University Medical Center reported online in Neurology.

Nor was there an association when statins were classified as more lipophilic (HR: 1.05, 95% CI: 0.57 to 1.95) or less lipophilic (HR: 0.71, 95% CI: 0.29 to 1.74).

Even though statins are widely prescribed, the researchers said, their effect on Alzheimer's disease remains murky because of conflicting study results.

So Dr. Arvanitakis' team turned to the Religious Orders Study, a prospective study of dementia among members of more than 40 Catholic religious groups across the U.S.

The researchers enrolled 929 older participants of the ongoing study (68.7% female, mean baseline age 74.9) from January 1994 through November 2006.

All participants agreed to yearly clinical visits to be evaluated for statin use and signs of Alzheimer's disease, dementia, or cognitive decline. In addition, they agreed to a brain autopsy at death to assess signs of disease pathology.

Global cognition was measured using 19 tests (seven for episodic memory, four for semantic memory, four for working memory, two for perceptual speed, and two for visuospatial ability).

Signs of Alzheimer's pathology included neuritic plaques, diffuse plaques, and neurofibrillary tangles. A global Alzheimer's disease pathology score was created by averaging the summary scores of the three markers.

Separate measures of amyloid and tangles were also assessed immunohistochemically.

At baseline, 119 (12.8%) of the participants were statin users. They were significantly younger than nonusers (72.7 versus 75.2, P<0.01) but similar in gender, education level, and cognition (P>0.11 for all).

Statin use showed no association with level of (P>0.08) or change in (P>0.20) global cognition, the researchers said.

Among participants who developed dementia, statin use also was not related to change in global cognition (P=0.32).

During the study, 314 participants died. Pathologic data were analyzed from the first consecutive 262 brain autopsies.

Almost all the deceased participants showed signs of Alzheimer's pathology and the mean global pathology score was similar between statin users and nonusers (0.59 [range 0 to 1.50] in users versus 0.70 [range 0 to 1.59] in nonusers, P=0.07).

The researchers collected amyloid data in 199 of the deceased. Most of them had amyloid immunoreactivity (mean value 1.79 units, range: 0 to 10.33). Statin users had significantly less immunoreactivity than nonusers (0.92 versus 1.97 units, P<0.001).

Use of more lipophilic statins, specifically simvastatin and lovastatin, were significantly associated with a lower likelihood of amyloid presence compared with use of the less lipophilic agents atorvastatin, pravastatin, and fluvastatin (P=0.03).

However, the researchers did not find associations between all statins (P=0.13), or more (P=0.73) or less (P=0.09) lipophilic agents and the continuous measure of amyloid load.

"Our data of an inverse association of statins with amyloid (dichotomized as present versus absent), and noted only in those using more lipophilic but not less lipophilic statins may be supportive of a possible protective effect of statins against â€¦ amyloid," they wrote.

"However, we did not find a relation of statins with a continuous measure of amyloid, raising the possibility of a spurious finding."

The researchers found no relation of statins to tangles (P=0.88).

They cautioned that interpretation of their results should be done carefully because of the small number of participants who used statins and later developed Alzheimer's disease.

They also acknowledged that the statin exposure in the study was nonrandom and that their results need to be replicated in a more diverse study population.

However, they said, "the cohort homogeneity may, in fact, control for effects of potential confounding factors (e.g., access to health care)."

The study was supported by grants from the National Institute on Aging.

The authors reported no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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